Animal models will be utilized to evaluate gene transfer into hematopoietic stem cells and its influence on hemoglobin synthesis. This work involves collaboration between investigators at St. Jude Children's Research Hospital and within the Intramural Program at the National Institutes of Health. Unique immunodeficient, transgenic mice expressing the human cytokines, stem cell factor, interleukin-3, and granulocyte macrophage- colony stimulating factor are capable of sustaining human hematopoiesis for several weeks following injection of primitive cell populations which have been purified y immunological techniques. The efficiency of various vector systems for insertion of genes into such cells will be evaluated. Transcriptional units, either a globin gene or cDNA sequences designed to increase or decrease activity of a specific transcriptional factors, will be introduced to determine the effect on hemoglobin synthesis in maturing erythroblasts derived from these primitive cell populations in vivo. When appropriate, analogous experiments will be performed in a simian gene transfer, autologous bone marrow transplantation model using an experimental design which is potentially clinically applicable. The capacity for gene insertion into true repopulating stem cells will be best determined in this primate transplantation model.